The occurrence of white matter (WM) abnormalities in psychotic disorders has been suggested by several studies investigating brain pathology and diffusion tensor measures, but evidence assessing regional WM morphometry is still scarce and conflicting. In the present study, 122 individuals with first-episode psychosis (FEP) (62 fulfilling criteria for schizophrenia/schizophreniform disorder, 26 psychotic bipolar I disorder, and 20 psychotic major depressive disorder) underwent magnetic resonance imaging, as well as 94 epidemiologically recruited controls. Images were processed with the Statistical Parametric Mapping (SPM2) package, and voxel-based morphometry was used to compare groups (t-test) and subgroups (ANOVA). Initially, no regional WM abnormalities were observed when both groups (overall FEP group versus controls) and subgroups (i.e., schizophrenia/schizophreniform, psychotic bipolar I disorder, psychotic depression, and controls) were compared. However, when the voxelwise analyses were repeated excluding subjects with comorbid substance abuse or dependence, the resulting statistical maps revealed a focal volumetric reduction in right frontal WM, corresponding to the right middle frontal gyral WM/third subcomponent of the superior longitudinal fasciculus, in subjects with schizophrenia/schizophreniform disorder (n = 40) relative to controls (n = 89). Our results suggest that schizophrenia/schizophreniform disorder is associated with right frontal WM volume decrease at an early course of the illness.
The cerebral white matter (WM) subserves all cognitive and neurological functions through its fiber pathways of axonal connections, constituting distributed neural circuits which link geographically distant regions in cortical and subcortical areas (Schmahmann et al., 2008). Lesions affecting the cerebral WM may result in a number of neuropsychiatric manifestations, and WM abnormalities have been reported to be associated with both psychotic and affective disorders (Walterfang et al., 2006 and Zanetti et al., 2009). Post-mortem studies found reductions in size and density of oligodendrocytes and abnormal myelin structure and compactness in the WM of schizophrenia patients ( Walterfang et al., 2006), whereas glial cell abnormalities have been observed in the brain of bipolar disorder (BD) subjects ( McDonald et al., 2004).
Major improvements in neuroimaging techniques have been seen during the past decades, which have allowed increasingly more detailed assessments of structural and functional aspects of the human brain in vivo ( Busatto et al., 2008). T1-weighted magnetic resonance images allow us to assess total or regional WM volumes ( Hulshoff Pol et al., 2004 and Plaze et al., 2011), while the more recently developed diffusion tensor imaging (DTI) provides us measures of anisotropy (a measure of fiber density and myelination) and diffusivity (an estimate of the displacement of water molecules in a tissue) ( Zanetti et al., 2009).
DTI studies support the existence of WM brain abnormalities in both psychotic and affective disorders (Zanetti et al., 2009 and Bora et al., 2011). Two meta-analyses of DTI studies found schizophrenia to be consistently associated with fractional anisotropy reductions in fronto-limbic-striatal WM (Ellison-Wright and Bullmore, 2009 and Bora et al., 2011), specially involving the inferior fronto-occipital and longitudinal fasciculi bilaterally, which were observed to be affected even in first-episode patients (Bora et al., 2011). In affective disorders, studies employing DTI techniques have also revealed microstructural WM abnormalities affecting fronto-limbic-striatal circuits (Zanetti et al., 2009, Korgaonkar et al., 2011 and Vederine et al., 2011). However, the anatomical regions most frequently implicated in bipolar disorder (BD) have been the ventromedial prefrontal WM, and the uncinate and superior longitudinal fasciculi (Zanetti et al., 2009 and Vederine et al., 2011), whereas a pattern of limbic-dorsolateral prefrontal-parietal WM abnormalities has been described for major depressive disorder (MDD) (Ma et al., 2007, Wu et al., 2011 and Korgaonkar et al., 2011).
